Phospholipases and their metabolites in cancer

Phospholipids are the fundamental component of biological membranes present in all living cells. Phospholipases are the lipolytic enzymes that hydrolyze particular ester linkages in phospholipids and produce a variety of bioactive lipid mediators including diacylglycerol, phosphatidic acid, lysophosphatidic acid, and arachidonic acid (AA). Phospholipases like phospholipases (A1 and A2), phospholipases C, and phospholipases D are important intercellular and intracellular signaling mediators that have a wide range of structures, functions, and mechanisms in cancer biology. Multiple cellular activities (proliferation, migration, invasion, and angiogenesis) that promote cancers are regulated by several lipid mediators. Mechanisms of individual phospholipases, by which these influence cancer-related cellular activities and the interplay between them, have been investigated by researchers. Choline kinase, phosphatidylcholine-specific phospholipase D1, phosphatidylcholine-specific phospholipase C, sphingomyelinases, choline transporters, phosphodiesterases, phosphatidylethanolamine, N-methyltransferase, and ethanolamine kinase are the significant phospholipases in carcinogenesis. These enzymes are attributed to oncogenic transformation, tumor growth, and critical cancer cell characteristics such as fast proliferation, migration, and invasion. This chapter aims to explore the current understanding of phospholipase categorization and mechanism in cancer biology. The present literature also discusses potential mechanistic and therapeutic targets.